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Pediatric Surgery International

, Volume 35, Issue 12, pp 1353–1361 | Cite as

An intra-amniotic injection of mesenchymal stem cells promotes lung maturity in a rat congenital diaphragmatic hernia model

  • Shohei TakayamaEmail author
  • Kohei Sakai
  • Shigehisa Fumino
  • Taizo Furukawa
  • Tsunao Kishida
  • Osam Mazda
  • Tatsuro Tajiri
Original Article
  • 71 Downloads

Abstract

Purpose

We aimed to evaluate the effect of human mesenchymal stem cells (hMSCs) on congenital diaphragmatic hernia (CDH) by intra-amniotic injection in a rat CDH model.

Methods

Nitrofen (100 mg) was administered to pregnant rats at E9.5. hMSCs (1.0 × 106) or PBS was injected into each amniotic cavity at E18, and fetuses were harvested at E21. The fetal lungs were classified into normal, CDH, and CDH-hMSCs groups. To determine the lung maturity, we assessed the alveolar histological structure by H&E and Weigert staining and the alveolar arteries by Elastica Van Gieson (EVG) staining. TTF-1, a marker of type II alveolar epithelial cells, was also evaluated by immunohistochemical staining and real-time reverse transcription polymerase chain reaction.

Results

The survival rate after intra-amniotic injection was 72.1%. The CDH-hMSCs group had significantly more alveoli and secondary septa than the CDH group (p < 0.05). The CDH-hMSCs group had larger air spaces and thinner alveolar walls than the CDH group (p < 0.05). The medial and adventitial thickness of the pulmonary artery in the CDH-hMSCs group were significantly better (p < 0.001), and there were significantly fewer TTF-1-positive cells than in the CDH group (p < 0.001).

Conclusion

These results suggest that intra-amniotic injection of hMSCs has therapeutic potential for CDH.

Keywords

Congenital diaphragmatic hernia Mesenchymal stem cell Intra-amniotic injection Fetal therapy Lung hypoplasia Nitrofen 

Notes

Acknowledgements

This work was supported in part by Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI grant number 15K10926 [TF]). The English used in this manuscript was reviewed by Brian Quinn (Editor-in-Chief, Japan Medical Communication).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Shohei Takayama
    • 1
    • 2
    Email author
  • Kohei Sakai
    • 1
  • Shigehisa Fumino
    • 1
  • Taizo Furukawa
    • 1
  • Tsunao Kishida
    • 2
  • Osam Mazda
    • 2
  • Tatsuro Tajiri
    • 1
  1. 1.Department of Pediatric SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of ImmunologyKyoto Prefectural University of MedicineKyotoJapan

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